"In their own words": delineating the contours of dyspnea invisibility in patients with advanced chronic obstructive pulmonary disease from quantitative discourse analysis.

BACKGROUND: Dyspnea conveys an upsetting or distressing experience of breathing awareness. It heavily weighs on chronic respiratory disease patients, particularly when it persists despite maximal treatment of causative abnormalities. The physical, psychological and social impacts of persistent dyspnea are ill-appreciated by others. This invisibility constitutes a social barrier and impedes access to care. This study aimed to better understand dyspnea invisibility in patients with chronic obstructive pulmonary disease (COPD) through quantitative discourse analysis. METHODS: We conducted a lexicometric analysis (lemmatization, descending hierarchical classification, multicomponent analysis, similarity analysis) of 11 patients' discourses (6 men, severe COPD; immediate postexacerbation rehabilitation) to identify semantic classes and communities, which we then confronted with themes previously identified using interpretative phenomenological analysis (IPA). RESULTS: Class#1 ("experience and need for better understanding"; 38.9% of semantic forms, 50% of patients) illustrates the gap that patients perceive between their experience and what others see, confirming the importance of dyspnea invisibility in patients' concerns. Class#2 ("limitations"; 28.7% of forms) and Class#3 (management"; 13.1% of forms) point to the weight of daily limitations in performing basic activities, of the need to accept or adapt to the constraints of the disease. These three classes matched previously identified IPA-derived themes. Class#4 ("hospitalization"; 18.2% of forms) points to the importance of interactions with the hospital, especially during exacerbations, which constitutes novel information. CONCLUSIONS: Lexicometry confirms the importance of dyspnea invisibility as a burden to COPD patients.

Diaphragm Neurostimulation Assisted Ventilation in Critically Ill Patients.

Diaphragm neurostimulation consists of placing electrodes directly on or in proximity to the phrenic nerve(s) to elicit diaphragmatic contractions. Since its initial description in the 18th century, indications have shifted from cardiopulmonary resuscitation to long-term ventilatory support. Recently, the technical development of devices for temporary diaphragm neurostimulation has opened up the possibility of a new era for the management of mechanically ventilated patients. Combining positive pressure ventilation with diaphragm neurostimulation offers a potentially promising new approach to the delivery of mechanical ventilation which may benefit multiple organ systems. Maintaining diaphragm contractions during ventilation may attenuate diaphragm atrophy and accelerate weaning from mechanical ventilation. Preventing atelectasis and preserving lung volume can reduce lung stress and strain and improve homogeneity of ventilation, potentially mitigating ventilator-induced lung injury. Furthermore, restoring the thoracoabdominal pressure gradient generated by diaphragm contractions may attenuate the drop in cardiac output induced by positive pressure ventilation. Experimental evidence suggests diaphragm neurostimulation may prevent neuroinflammation associated with mechanical ventilation. This review describes the historical development and evolving approaches to diaphragm neurostimulation during mechanical ventilation and surveys the potential mechanisms of benefit. The review proposes a research agenda and offers perspectives for the future of diaphragm neurostimulation assisted mechanical ventilation for critically ill patients.

'You can't feel what we feel': Multifaceted dyspnoea invisibility in advanced chronic obstructive pulmonary disease examined through interpretative phenomenological analysis.

BACKGROUND: More than a symptom, dyspnoea is an existential experience shaping the lives of those afflicted, particularly when its persistence despite maximal pathophysiological treatments makes it pervasive. It is, however, insufficiently appreciated by concerned people themselves, family members, healthcare professionals and the public (dyspnoea invisibility), limiting access to appropriate care and support. AIM: To provide a better understanding of dyspnoea experiences and its invisibility. DESIGN: Interpretative phenomenological analysis of data collected prospectively through in-depth semi-structured interviews. SETTING/PARTICIPANTS: Pulmonary rehabilitation facility of a tertiary care university hospital; 11 people (six men, five women) with severe chronic obstructive pulmonary disease (stages 3 and 4 of the 4-stage international GOLD classification) admitted for immediate post-exacerbation rehabilitation. RESULTS: We identified several types of dyspnoea invisibility depending on temporality and interlocutors: (1) invisibility as a symptom to oneself; (2) invisibility as a symptom to others; (3) invisibility as an experience that cannot be shared; (4) invisibility as an experience detached from objective measurements; (5) invisibility as an experience that does not generate empathic concern. The notion of invisibility was present in all the identified experiential dimensions of dyspnoea. It was seen as worsening the burden of the disease and as self-aggravating through self-isolation and self-censorship. CONCLUSIONS: The study confirmed that dyspnoea invisibility is a reality for people with advanced chronic obstructive pulmonary disease. It shows dyspnoea invisibility to be a multifaceted burden. Future research should aim at identifying individual and collective measures to overcome dyspnoea invisibility.

Abnormal Activity of Neck Inspiratory Muscles during Sleep as a Prognostic Indicator in Chronic Obstructive Pulmonary Disease.

Rationale: In patients with chronic obstructive pulmonary disease (COPD), increased activity of neck inspiratory muscles has been reported as a compensatory response to hyperinflation-related diaphragmatic dysfunction. The persistence of this activity during sleep could attenuate sleep-related hypoventilation and also negatively impact sleep and clinical outcomes.Objectives: To assess the persistence of neck-muscle activity during sleep in patients with COPD recovering from severe exacerbations (i.e., requiring hospitalization) and its impact on sleep quality and recurrence of exacerbations.Methods: Video polysomnography with neck-muscle EMG was performed in patients with COPD who were recovering from a severe exacerbation. The follow-up period lasted 6 months to record the next severe exacerbation.Measurements and Main Results: Twenty-nine patients were included in the study (median [25th-75th percentile] age, 71 [64-72] yr; 55% male; body mass index, 24 [21-29]; FEV1% predicted, 37 [29-45]; and BODE [body mass index, airflow obstruction, dyspnea, and exercise] index, 6 [5-7]). Twenty-six of these patients exhibited sleep-related neck-muscle activity, which was intermittent (limited to stage 3 sleep) in 17 and permanent throughout sleep in 9. α-Delta EEG activity during stage 3 sleep was observed in 87% of the patients. Compared with patients with no or intermittent neck-muscle activity, those with permanent neck-muscle activity showed more disrupted sleep, had experienced more exacerbations in the previous year, and suffered their next severe exacerbation earlier.Conclusions: Sleep-related neck-muscle activity occurs frequently in patients with COPD who are recovering from a severe exacerbation and seems to negatively affect sleep quality and prognosis; therefore, identification of this activity might improve COPD management after a severe exacerbation.

Framework for patient-ventilator asynchrony during long-term non-invasive ventilation.

Episodes of patient-ventilator asynchrony (PVA) occur during acute and chronic non-invasive positive pressure ventilation (NIV). In long-term NIV, description and quantification of PVA is not standardised, thus limiting assessment of its clinical impact. The present report provides a framework for a systematic analysis of polygraphic recordings of patients under NIV for the detection and classification of PVA validated by bench testing. The algorithm described uses two different time windows: rate asynchrony and intracycle asynchrony. This approach should facilitate further studies on prevalence and clinical impact of PVA in long-term NIV.

European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD.

BACKGROUND: While the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients. MATERIALS AND METHODS: The European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients. RESULTS: The task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode. CONCLUSIONS: Managing hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.

Human diaphragm atrophy in amyotrophic lateral sclerosis is not predicted by routine respiratory measures.

Amyotrophic lateral sclerosis (ALS) patients show progressive respiratory muscle weakness leading to death from respiratory failure. However, there are no data on diaphragm histological changes in ALS patients and how they correlate with routine respiratory measurements.We collected 39 diaphragm biopsies concomitantly with laparoscopic insertion of intradiaphragmatic electrodes during a randomised controlled trial evaluating early diaphragm pacing in ALS (https://clinicaltrials.gov; NCT01583088). Myofibre type, size and distribution were evaluated by immunofluorescence microscopy and correlated with spirometry, respiratory muscle strength and phrenic nerve conduction parameters. The relationship between these variables and diaphragm atrophy was assessed using multivariate regression models.All patients exhibited significant slow- and fast-twitch diaphragmatic atrophy. Vital capacity (VC), maximal inspiratory pressure, sniff nasal inspiratory pressure (SNIP) and twitch transdiaphragmatic pressure did not correlate with the severity of diaphragm atrophy. Inspiratory capacity (IC) correlated modestly with slow-twitch myofibre atrophy. Supine fall in VC correlated weakly with fast-twitch myofibre atrophy. Multivariate analysis showed that IC, SNIP and functional residual capacity were independent predictors of slow-twitch diaphragmatic atrophy, but not fast-twitch atrophy.Routine respiratory tests are poor predictors of diaphragm structural changes. Improved detection of diaphragm atrophy is essential for clinical practice and for management of trials specifically targeting diaphragm muscle function.

NIV in amyotrophic lateral sclerosis: The 'when' and 'how' of the matter.

Non-invasive ventilation (NIV) has become an essential part of the treatment of amyotrophic lateral sclerosis (ALS) since 2006. NIV very significantly improves survival, quality of life and cognitive performances. The initial NIV settings are simple, but progression of the disease, ventilator dependence and upper airway involvement sometimes make long-term adjustment of NIV more difficult, with a major impact on survival. Unique data concerning the long-term adjustment of NIV in ALS show that correction of leaks, management of obstructive apnoea and adaptation to the patient's degree of ventilator dependence improve the prognosis. Non-ventilatory factors also impact the efficacy of NIV and various solutions have been described and must be applied, including cough assist techniques, control of excess salivation and renutrition. NIV in ALS has been considerably improved as a result of application of all of these measures, avoiding the need for tracheostomy in the very great majority of cases. More advanced use of NIV also requires pulmonologists to master the associated end-of-life palliative care, as well as the modalities of discontinuing ventilation when it becomes unreasonable.

Impact of leaks and ventilation parameters on the efficacy of humidifiers during home ventilation for tracheostomized patients: a bench study.

BACKGROUND: During invasive ventilation, the upper airway is bypassed and no longer participates in humidification of inspired gases, which is essential to avoid harmful consequences such as endotracheal tube occlusion. In the case of increased air flow, especially in the presence of leaks (intentional or unintentional), the humidification provided by humidifiers may become ineffective. The objective of this bench study was to evaluate the quality of humidification provided by heated humidifiers under various home ventilation conditions. METHODS: Five heated humidifiers were tested in eight configurations combining circuit (expiratory valve or vented circuit), tidal volume (600 or 1000 mL) and presence of unintentional leak. Absolute humidity (AH) was measured at the upstream of the test lungs, which were placed in a 34 °C environmental chamber in order to simulate body temperature. RESULTS: The AH measured in the valve circuit ranged between 30 mg/L and 40 mg/L and three out of the five humidifiers achieved an AH higher than the recommended level (33 mg/L). With the vented circuit without unintentional leak, when tidal volume was set at 600 mL, all humidifiers reached an AH higher than 33 mg/L except one device; when the tidal volume was set at 1000 mL and unintentional leak was present, four out of the five humidifiers provided an AH lower than 33 mg/L. CONCLUSION: This study shows that, except under certain home ventilation conditions, such as high tidal volumes with unintentional leak in vented circuit, most heated humidifiers ensure sufficient humidification to avoid the risk of side effect in patients.

Flow and airway pressure analysis for detecting ineffective effort during mechanical ventilation in neuromuscular patients.

Ineffective efforts (IEs) are among the most common types of patient-ventilator asynchrony. The objective of this study is to validate IE detection during expiration using pressure and flow signals, with respiratory effort detection by esophageal pressure (Pes) measurement as the reference, in patients with neuromuscular diseases (NMDs). We included 10 patients diagnosed with chronic respiratory failure related to NMD. Twenty-eight 5-minute recordings of daytime ventilation were studied for IE detection. Standard formulas were used to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of IE detection using pressure and flow signals compared to Pes measurement. Mean sensitivity and specificity of flow and pressure signal-based IE detection versus Pes measurement were 97.5% ± 5.3% and 91.4% ± 13.7%, respectively. NPV was 98.1% ± 8.2% and PPV was 67.6% ± 33.8%. Spearman's rank correlation coefficient indicated a moderately significant correlation between frequencies of IEs and controlled cycles ( ρ = 0.50 and p = 0.01). Among respiratory cycles, 311 (11.2%) were false-positive IEs overall. Separating false-positive IEs according to their mechanisms, we observed premature cycling in 1.2% of cycles, delayed ventilator triggering in 0.1%, cardiac contraction in 9.2%, and upper airway instability during expiration in 0.3%. Using flow and pressure signals to detect IEs is a simple and rapid method that produces adequate data to support clinical decisions.

Relieving dyspnoea by non-invasive ventilation decreases pain thresholds in amyotrophic lateral sclerosis.

BACKGROUND: Dyspnoea is a threatening sensation of respiratory discomfort that presents many similarities with pain. Experimental dyspnoea in healthy subjects induces analgesia. This 'dyspnoea-pain counter-irritation' could, in reverse, imply that relieving dyspnoea in patients with chronic respiratory diseases would lower their pain thresholds. METHODS: We first determined pressure pain thresholds in 25 healthy volunteers (22-31 years; 13 men; handheld algometer), during unloaded breathing (BASELINE) and during inspiratory threshold loading (ITL). Two levels of loading were used, adjusted to induce dyspnoea self-rated at 60% or 80% of a 10 cm visual analogue scale (ITL6 and ITL8). 18 patients with chronic respiratory failure due to amyotrophic lateral sclerosis (ALS) were then studied during unassisted breathing and after 30 and 60 min of non-invasive ventilation-NIV30 and NIV60-(same dyspnoea evaluation). RESULTS: In healthy volunteers, pressure pain thresholds increased significantly in the deltoid during ITL6 (p<0.05) and ITL8 (p<0.05) and in the trapezius during ITL8 (p<0.05), validating the use of pressure pain thresholds to study dyspnoea-pain counter-irritation. In patients with ALS, the pressure pain thresholds measured in the deltoid during unassisted breathing decreased by a median of 24.5%-33.0% of baseline during NIV30 and NIV60 (p<0.05). CONCLUSION: Relieving dyspnoea by NIV in patients with ALS having respiratory failure is associated with decreased pressure pain thresholds. Clinical implications have yet to be determined, but this observation suggests that patients with ALS could become more susceptible to pain after the institution of NIV, hence the need for reinforced attention towards potentially painful diagnostic and therapeutic interventions.

Combined effects of leaks, respiratory system properties and upper airway patency on the performance of home ventilators: a bench study.

BACKGROUND: Combined effects of leaks, mechanical property of respiratory system and upper airway (UA) patency on patient-ventilator synchrony (PVA) and the level of clinically "tolerable" leaks are not well established in home ventilators. METHODS: We comparatively assessed on a bench model, the highest leak level tolerated without inducing significant asynchrony ("critical leak") in three home ventilators (Astral 150, Trilogy 100 and Vivo 60; noted as A150, T100 and V60 respectively) subjected to three simulated diseased respiratory conditions: chronic obstructive pulmonary disease (COPD), obesity hypoventilation (OHS) and neuromuscular disorders (NMD), with both open and closed UA. Also, total leak values in the device reports were compared to the bench-measured values. RESULTS: With open UA, all ventilators were able to avoid asynchrony up to a 30 L/min leak and even to 55 L/min in some cases. UA closure and respiratory diseases especially OHS influenced PVA. With closed UA, the critical leak of A150 and T100 remained higher than 55 L/min in COPD and OHS, while for V60 decreased to 41 and 33 L/min respectively. In NMD with closed UA, only T100 reached a high critical leak of 69 L/min. Besides, inspiratory trigger sensitivity change was often necessary to avoid PVA. CONCLUSIONS: Home ventilators were able to avoid PVA in high-level leak conditions. However, asynchrony appeared in cases of abnormal mechanical properties of respiratory system or closed UA. In case of closed UA, the EPAP should be adjusted prior to the inspiratory trigger. TRIAL REGISTRATION: Not applicable.

Sleep and Mechanical Ventilation in Stable COPD Patients.

Respiratory work is physiologically increased during sleep and leads to severe alterations in COPD patients, especially by raising sleep hypoventilation. The diurnal impact of these nocturnal events may have been underestimated in COPD patients. Impaired sleep and the increase of respiratory work may be one of the major trigger of diurnal events like hypoventilation, exacerbation and even mortality. One of the most commonly used nocturnal treatments at the present time is noninvasive ventilation (NIV). However, there is an on-going debate concerning the indications and objectives of NIV in COPD patients. In most studies, NIV initiation and monitoring depend on diurnal tools like PaCO2, and the nocturnal efficacy of this treatment has not yet been adequately determined. In other respiratory diseases, sleep events have a predominant role in NIV therapy. Such nocturnal events drive NIV initiation and setting adaptation. Monitoring of sleep events is associated with an increase in health related to quality of life and a decrease in mortality. The monitoring may be the solution to solve the debate of NIV in COPD patients. This article reviews the impact of sleep in COPD patients and the value of long-term NIV.

Cortical drive to breathe in amyotrophic lateral sclerosis: a dyspnoea-worsening defence?

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing diaphragm weakness that can be partially compensated by inspiratory neck muscle recruitment. This disappears during sleep, which is compatible with a cortical contribution to the drive to breathe. We hypothesised that ALS patients with respiratory failure exhibit respiratory-related cortical activity, relieved by noninvasive ventilation (NIV) and related to dyspnoea.We studied 14 ALS patients with respiratory failure. Electroencephalographic recordings (EEGs) and electromyographic recordings of inspiratory neck muscles were performed during spontaneous breathing and NIV. Dyspnoea was evaluated using the Multidimensional Dyspnea Profile.Eight patients exhibited slow EEG negativities preceding inspiration (pre-inspiratory potentials) during spontaneous breathing. Pre-inspiratory potentials were attenuated during NIV (p=0.04). Patients without pre-inspiratory potentials presented more advanced forms of ALS and more severe respiratory impairment, but less severe dyspnoea. Patients with pre-inspiratory potentials had stronger inspiratory neck muscle activation and more severe dyspnoea during spontaneous breathing.ALS-related diaphragm weakness can engage cortical resources to augment the neural drive to breathe. This might reflect a compensatory mechanism, with the intensity of dyspnoea a negative consequence. Disease progression and the corresponding neural loss could abolish this phenomenon. A putative cognitive cost should be investigated.

Reduced survival in patients with ALS with upper airway obstructive events on non-invasive ventilation.

INTRODUCTION: Non-invasive ventilation (NIV) is part of standard care in amyotrophic lateral sclerosis (ALS). Intolerance or unavailability of NIV, as well as the quality of correction of nocturnal hypoventilation, has a direct impact on prognosis. OBJECTIVES: We describe the importance of NIV failure due to upper airway obstructive events, the clinical characteristics, as well as their impact on the prognosis of ALS. METHODS: Retrospective analysis of the data of 190 patients with ALS and NIV in a single centre for the period 2011-2014. 179 patients tolerating NIV for more than 4 h per night without leaks were analysed. RESULTS: Among the 179 patients, after correction of leaks, 73 remained inadequately ventilated at night (defined as more than 5% of the night spent at <90% of SpO2), as a result of obstructive events in 67% of cases (n=48). Patients who remained inadequately ventilated after optimal adjustment of ventilator settings presented with shorter survival than adequately ventilated patients. Unexpectedly, patients with upper airway obstructive events without nocturnal desaturation and in whom no adjustment of treatment was therefore performed also presented with shorter survival. On initiation of NIV, no difference was demonstrated between patients with and without upper airway obstructive events. In all patients, upper airway obstruction was concomitant with reduction of ventilatory drive. CONCLUSIONS: This study shows that upper airway obstruction during NIV occurs in patients with ALS and is associated with poorer prognosis. Such events should be identified as they can be corrected by adjusting ventilator settings.

Health-related quality of life in young adults with congenital central hypoventilation syndrome due to PHOX2B mutations: a cross-sectional study.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disease due to PHOX2B mutations. CCHS patients suffer from many autonomic disorders, dominated clinically by defective ventilatory automatisms. From birth, the life of CCHS patients depends on ventilatory support during sleep, involving a high burden of care. Whether or not this impairs the quality of life of these patients during adulthood remains unknown. METHODS: We applied the medical outcome study short form-36 (SF-36) to 12 CCHS patients aged 15-33 (9 women) at the time of their passage from pediatric to adult care. Scores for the SF-36 dimensions were compared to the age- and gender-matched French reference population after transformation into standardized Z-scores. The SF-36 physical component summary score (PCS) and mental component summary score (MCS) were compared to American reference values. RESULTS: Median Z-scores were significantly different from zero for PF (physical functioning, p = 0.020) and GH (general health perception, p = 0.0342) and for PCS (p = 0.020). The other physical dimensions (RP, role limitation due to physical function; BP, bodily pain) and the mental dimensions (VT, vitality; SF, social functioning; RE, role limitation due to emotional function; MH, mental health) and MCS were not altered. CONCLUSIONS: We conclude that, despite the physical constraints imposed by CCHS and its anxiogenic nature, this disease is associated with an impairment of health-related quality of life in young adults that remains moderate. Whatever the underlying explanations, these results convey hope to parents with a child diagnosed with CCHS and for patients themselves.

A novel technique for diaphragm biopsies in human patients.

BACKGROUND: The diaphragm is difficult to biopsy because of its anatomic location. We describe a new laparoscopic diaphragm biopsy technique. MATERIAL AND METHODS: Fifty one patients with amyotrophic lateral sclerosis gave their consent to diaphragm biopsy in the context of an implanted phrenic nerve stimulation protocol (NCT01583088). The biopsy was taken from the costal diaphragm, after opening the parietal peritoneum with scissors, and by grasping the diaphragmatic muscle over the rib with toothed laparoscopy forceps. RESULTS: The first four electrocoagulation biopsies were unsuitable for morphologic examination. The following 47 biopsies were therefore performed without electrocoagulation. The mean size of the biopsy fragments obtained after preparation was 3 ± 1 × 2 ± 1 × 1 ± 1 mm (maximum: 4 × 3 × 2 mm). A diaphragmatic injury occurred during the section in three cases requiring immediate suture without causing pneumothorax. A small pleural effusion was observed on the postoperative chest x-ray in one patient with a spontaneously favorable outcome. Numerous stains were able to be performed on the fragments obtained. CONCLUSIONS: Diaphragm biopsy can be safely performed by laparoscopy and yields tissue suitable for our future histologic evaluation.